ADC Therapeutics Eyes ZYNLONTA Expansion as LOTIS-5 Data Nears

Company focuses on moving ZYNLONTA into earlier lines of DLBCL and indolent lymphomas

Mar. 27, 2026 at 12:33am

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ADC Therapeutics executives outlined the company's strategy to expand the reach of its CD19-directed antibody-drug conjugate ZYNLONTA (loncastuximab tesirine) beyond its current third-line-plus diffuse large B-cell lymphoma (DLBCL) approval. The company is focused on moving ZYNLONTA into earlier lines of DLBCL and into indolent lymphomas, with two key studies - LOTIS-5 and LOTIS-7 - aimed at the second-line-plus setting.

Why it matters

Expanding ZYNLONTA's reach beyond third-line DLBCL is crucial for ADC Therapeutics to maximize the value of its core asset. The company sees significant growth potential in moving into the second-line setting, where it expects ZYNLONTA to demonstrate improved efficacy and safety compared to the current standard of care.

The details

LOTIS-5 is a 420-patient, 1:1 randomized Phase III study evaluating ZYNLONTA plus rituximab versus R-GemOx (rituximab, gemcitabine, oxaliplatin) in second-line, transplant-ineligible DLBCL. The trial is powered to demonstrate a hazard ratio of 0.67 or lower on the primary endpoint of progression-free survival. LOTIS-7 is a Phase Ib study combining ZYNLONTA with the CD20xCD3 bispecific glofitamab in second-line-plus DLBCL, showing high response rates and a manageable safety profile.

  • The company expects LOTIS-5 top-line data in the second quarter of 2026.
  • If LOTIS-5 results are positive, ADC Therapeutics anticipates filing a supplemental BLA roughly four to five months after the readout, followed by an expected 10-month standard review - timing that would imply a potential approval around mid-2027.

The players

ADC Therapeutics

A clinical-stage biopharmaceutical company focused on the discovery and development of highly targeted antibody-drug conjugates (ADCs) to treat hematological malignancies.

Ameet Mallik

Chief Executive Officer of ADC Therapeutics.

ZYNLONTA

ADC Therapeutics' CD19-directed antibody-drug conjugate that is currently approved as a monotherapy for third-line-plus diffuse large B-cell lymphoma (DLBCL).

LOTIS-5

A Phase III confirmatory trial evaluating ZYNLONTA plus rituximab versus R-GemOx (rituximab, gemcitabine, oxaliplatin) in second-line, transplant-ineligible DLBCL.

LOTIS-7

A Phase Ib study combining ZYNLONTA with the CD20xCD3 bispecific glofitamab in second-line-plus DLBCL.

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What they’re saying

“The real growth opportunity starts when we move into the second-line setting.”

— Ameet Mallik, Chief Executive Officer, ADC Therapeutics

What’s next

The judge in the case will decide on Tuesday whether or not to allow Walker Reed Quinn out on bail.

The takeaway

Expanding ZYNLONTA into earlier lines of DLBCL and indolent lymphomas is crucial for ADC Therapeutics to maximize the value of its core asset. The upcoming LOTIS-5 and LOTIS-7 data readouts will be key events that could significantly de-risk the company's growth opportunity starting in 2027.